Treatment and prognosis of patients with urinary
bladder cancer with other primary cancers: a
nationwide population-based study in the Bladder
Cancer Data Base Sweden (BladderBaSe)
Firas Aljabery1 , Fredrik Liedberg2,3, Christel H€aggstr€om4,5, Viveka Str€ock6,7, Abolfazl Hosseini8, Truls Gardmark9, Amir Sherif10, Tomas Jerlstr€om11, Per-Uno Malmstr€om4 , Oskar Hagberg3and Lars Holmberg4,12
1Division of Urology, Department of Clinical and Experimental Medicine, Link €oping University, Link €oping,2Department of Urology, Skane University Hospital, Malm€o,3Department of Translational Medicine, Lund University, Malm€o, 4Department of Surgical Sciences, Uppsala University, Uppsala,5Department of Biobank Research, Umea University, Umea,6Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg,7Department of Urology, Region V €astra G €otaland, Sahlgrenska University Hospital, Gothenburg,
8Department of Pelvic Cancer, Karolinska University Hospital, Stockholm,9Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm,10Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea,11Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, €Orebro University, €Orebro, Sweden, and12School of Medicine, King’s College London, London, UK
Objective
To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.
Patients And Methods
Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the
probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997–2014 with or without OPC. The analyses considered the patient’s characteristics, UBC tumour stage at diagnosis, and site of OPC.
Results
There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.
Conclusions
OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.
Keywords
bladder cancer, other primary cancer, cohort study, management, outcome, #uroonc, #BladderCancer, #blcsm, #utuc
Introduction
The occurrence of urinary bladder cancer (UBC) after or in combination with another primary cancer (OPC) is a common clinical problem, which is becoming more frequent as survival after/in many cancers improves. In Northern Europe, UBC is the fourth most common secondary primary malignancy after a previous cancer diagnosis, constituting 10% of all secondary malignancies [1]. Consistent with these data, Surveillance, Epidemiology and End Results (SEER) data show that UBC as a new primary is common after cancers associated with smoking [2,3]. Epidemiological studies indicate that some cancer therapies, such as
cyclophosphamide and pelvic radiotherapy (RT), may induce UBC as a secondary primary [4,5].
While there is literature reporting on the occurrence of UBC after cancer at other sites [1,4], there has to our knowledge been no study to inform about treatment and prognosis for patients with UBC and a synchronous or metachronous OPC. An earlier or concomitant cancer may influence and limit treatment possibilities, as previous treatments can have delivered maximum doses of RT or selected chemotherapeutic drugs or may have caused side-effects resulting in
contraindications to treatment. Furthermore, having two or more malignancies may signal a reduced host resistance to cancer, which can lead to worse prognosis than in patients with UBC only. Thus, a previous cancer diagnosis may for several reasons influence clinical decision-making, so that management diverges from clinical guidelines. Our present study hypothesis was that patients with UBC and a synchronous or metachronous OPC had a worse prognosis than patients with UBC only, and we thus studied the stage of disease at diagnosis, the given treatment, the prognosis and causes of death in 9804 patients with UBC and OPC as compared to 28 885 patients with UBC as thefirst primary.
Patients And Methods
The study cohort consisted of all patients with UBC reported in the Bladder Cancer Data Base Sweden (BladderBaSe) from 1 January 1997 to 31 December 2014. The BladderBaSe was initiated in 2015 with the linkage of the Swedish National Registry for Urinary Bladder Cancer (SNRUBC) to a number of healthcare and demographic registers in Sweden [6]. The project was approved by the Research Ethics Board at Uppsala University, Sweden (EPN Reference number; 2015/ 277). Data on UBC included patient and tumour
characteristics and primary treatment. Clinical TNM stage was based on CT and/or MRI examinations and pathological examination of the transurethral resection of bladder specimen from the bladder tumour. Data on OPC included primary tumour site and date of diagnosis. The diagnosis of OPC was based on the morphological codes according to the WHO International Classification of Diseases for Oncology,
using ICD-7 and ICD-10 classifications. The codes were retrieved from the National Cancer Registry to which both pathological and clinical departments in Sweden have been bound by law to continuously report on all cases of newly diagnosed cancer since 1958.
The Charlson Comorbidity Index (CCI) was calculated from the codes in the Swedish Patient Register based on a list of diseases with a specific weight assigned to each disease category. The separate weights are collated to an overall score, categorised into: 0 for no comorbidity, 1 for mild comorbidity, 2 for intermediate, and≥3 for severe
comorbidity [6]. Marital status was categorised as married or non-married, with the latter category including never married, widowed and divorced patients. Educational level was categorised as low (≤9 years of primary school level), intermediate (10–12 years secondary school level), and high (≥13 years university level), corresponding to mandatory school, high school, and college or university. Date and cause of death were obtained from the Cause of Death Register and death from UBC was defined as ICD-7 code 1810 or 1816 and ICD-10 code C67 as underlying death cause. Curative treatment was considered to be radical cystectomy (RC) or RT with curative intent.
Definitions
OPC was defined as another cancer detected before or concomitantly with the diagnosis of UBC. The OPC group was further subdivided into metachronous and synchronous cancers. We used the International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC), which suggests an interval of 6 months to distinguish between synchronous and metachronous cancers if they arise at different sites [7,8]. Thus, synchronous OPC was defined as another cancer detected within 6 months before or after the diagnosis of UBC. Metachronous OPC was defined as another primary cancer detected more than 6 months before the diagnosis of UBC. OPCs according ICD-7 and ICD-10 codes are shown in Table S1. Stratification of OPC was performed as follows: respiratory tract cancer (including larynx and lung), gastro-intestinal (GI) tract cancer (sub-stratified in in upper and lower GI tumours), male genital cancer (including prostate cancer, testicular cancer, and penile cancer), female genital cancer (including uterine cervix cancer, uterus cancer, and ovarian cancer), urinary tract cancer (including renal, renal pelvis, ureter, and urethra), skin cancer (including melanoma and
non-melanoma skin cancer) and haematological cancer (including lymphoma and leukaemia) for further analyses.
Statistics
Differences in the distribution of covariates and in the probability of receiving treatment with curative intent
between groups were statistically tested using the chi-squared test. P values<0.05 were considered to be statistically significant. Uni- and multivariate Cox regression survival analyses adjusted for age at diagnosis, marital status, education, year of diagnosis, CCI and T-stage were used to compare UBC-specific survival and overall survival (OS) between groups. In the survival analyses, the starting date was the date of UBC diagnosis, and last date of the study was either the date of death, emigration, or the administrative date of the end of follow-up (31 December 2014), whichever happened first.
Results
Of 38 689 participants in the BladderBaSe cohort, 2503 (6.5%) had a synchronous OPC and 7301 (19%) individuals had a metachronous OPC. The median (interquartile range) follow-up was 2.3 (0.9–5.8) years.
Patient Characteristics For Patients With OPC Vs Those With UBC Only
Compared to UBC-only patients, patients with synchronous OPC were more often male, older, had a higher CCI score, and had a higher proportion of T2 tumours, but a similar distribution of clinical node and distant metastases status (Table 1). Patients with metachronous OPC were more often female, older, and had a higher CCI score, but a similar stage distribution as patients with UBC only. Patients with
synchronous OPC were more often unmarried, but otherwise the socio-economic status was similar for the groups. For both patients with synchronous and metachronous OPC the distribution over diagnosis periods was skewed towards later time periods: the proportion of all patients with UBC with synchronous or metachronous OPC increased from 5.5% and 16% to 7% and 22% respectively from 1997–2001 to 2011– 2014.
Curative Treatment Offered
Treatment of UBC with curative intent (RC or RT) was given more often to patients with synchronous OPC as compared to patients with UBC only (Tables 2 and 3). Table 2 shows that this pattern was especially marked for men, younger individuals and patients with more favourable stages, and also for 861/5164 (17%) patients with non-muscle-invasive disease received such treatment. For patients with metachronous OPC, the probability of being offered treatment with curative intent was lower for those with T2–4 compared to those with UBC only: 33% vs 42% were offered such treatment.
Looking at organ system of OPC as a determinant of being offered treatment with curative intent, it was mainly men with synchronous prostate cancer that were offered such
treatment. Also, patients with synchronous female genital cancer and lower GI cancer were more often treated with curative intent than patients with UBC only (Table 3). Survival and Causes of Death
When UBC-specific survival for all patients with synchronous OPC was compared with that for patients with UBC only in a Cox regression model adjusted for gender, age at diagnosis, education, marital status, year of diagnosis, CCI category and T-stage, survival was 22% better in relative terms for those with synchronous OPC (Table 4); however, OS was similar (Tables 4 and 5). The distribution of patient characteristics and differences in treatment patterns motivated further survival analyses that were stratified by gender and called for one analysis where men with synchronous prostate cancer were excluded. The estimates from those models show that it was mainly the men with synchronous prostate cancer that drove the trend for patients with synchronous OPC to do better in UBC-specific survival (Table 4). The prognosis for men with synchronous prostate cancer also influenced the estimates of OS; when women and men (excluding those with synchronous prostate cancer) were looked at separately, patients with synchronous OPC had a worse OS (relative hazards [95% CI] of 1.27 [1.06–1.54] and 1.46 [1.31–1.63] respectively; Table 4). Patients with metachronous OPC had estimates of relative hazards for UBC-specific and OS close to unity, with small CIs when compared to patients with UBC only. A further study of the vital status and causes of death in the patients with OPC showed that it was the cancers with known worse prognosis that conferred the greater overall risk of death (Table 5).
Discussion
In all, 25% of all patients diagnosed with UBC had a metachronous or synchronous OPC. Patients with OPC were older and had more comorbidities. A larger proportion of the patients with synchronous OPC were men, while the opposite was true for patients with metachronous OPC compared to patients with UBC only. Those individuals with synchronous OPC more often had stage T2 and T3 tumours at diagnosis than those with UBC only. Patients with synchronous OPC in the prostate, female genital tract and lower GI tract were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, CCI and clinical T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in those OPCs that have a bad prognosis.
Metachronous and synchronous OPC in patients with UBC is a common clinical situation, e.g. in Germany and Sweden
UBC is the fourth most common second primary malignancy after another primary cancer [1]. Estimates from French cancer registries imply a similar situation with e.g. a 10.5% and 11.3% cumulative incidence of UBC in men at 10 years after afirst diagnosis of lung and prostate cancer, respectively [9]. UBC as a secondary primary malignancy is especially
common after cancers of the lung and bronchus, head and neck and stomach cancer, with which there is a shared strong association with tobacco smoking [1–3]. There is also a biological rationale to explain the association seen with a previous treatment for some cancers such as breast, prostate, rectal, and gynaecological cancers where treatments with Table 1 Patients with OPCs in the cohort of population-based UBC in Sweden 1997–2014.
Variable,n (%) OPC+ UBC UBC only,
n = 28 885 Total, N = 38 689 P Synchronous,n = 2503 Metachronous,n = 7301 Gender Male 2210 (88) 4753 (65) 21 880 (76) 28 843 (75) Female 293 (12) 2548 (35) 7005 (24) 9846 (25) <0.001
Age group, years
≤60 258 (10) 498 (7) 4892 (17) 5648 (15) 61–70 717 (29) 1527 (21) 7817 (27) 10 061 (26) 71–80 1073 (43) 2816 (38) 9696 (34) 13 585 (35) >80 544 (18) 2457 (34) 6461 (22) 9373 (24) <0.001 Social status Unmarried 881 (35) 2970 (41) 11 438 (40) 15 289 (40) Married 1622 (65) 4331 (59) 17 447 (60) 23 400 (60) <0.001 Education Low 1158 (46) 3381 (46) 12 984 (45) 17 523 (45) Intermediate 863 (35) 2478 (34) 10 111 (35) 13 452 (35) High 405 (16) 1206 (17) 4763 (16) 6374 (16) Missing 77 (3) 236 (3) 1027 (4) 1340 (4) 0.242 CCI 0 1255 (50) 2156 (30) 19 207 (67) 22 618 (59) 1 320 (13) 717 (10) 5508 (19) 6545 (17) 2 552 (22) 2420 (33) 2214 (8) 5186 (13) ≥3 376 (15) 2008 (27) 1956 (7) 4340 (11) <0.001 Healthcare region Stockholm 454 (18) 1358 (18) 5125 (18) 6937 (18) Uppsala/ €Orebro 511 (20) 1411 (19) 6245 (22) 8167 (21) South-East 257 (10) 846 (12) 3397 (12) 4500 (12) South 555 (22) 1635 (22) 5958 (21) 8148 (21) West 494 (20) 1435 (20) 5407 (19) 7336 (19) North 232 (9) 616 (8) 2753 (9) 3601 (9) <0.001 Diagnosis periods 1997–2001 536 (21) 1500 (21) 7587 (26) 9623 (25) 2002–2005 511 (20) 1411 (19) 6259 (22) 8181 (21) 2006–2010 758 (30) 2216 (30) 8070 (28) 11 044 (29) 2011–2014 698 (28) 2174 (30) 6969 (24) 9841 (25) <0.001 cT-stage TX 67 (3) 195 (3) 665 (2) 927 (2) Ta, T1,Tis 1462 (58) 5177 (71) 21 302 (74) 27 941 (72) T2–T4 974 (40) 1879 (26) 6918 (24) 9821 (25) <0.001 cN-stage N0 964 (39) 1922 (26) 7955 (28) 10 841 (28) N+ 129 (5) 232 (3) 1006 (4) 1367 (4) Nx 1410 (56) 5147 (71) 19 924 (69) 26 481 (68) <0.001 cM-stage M0 1047 (42) 1924 (26) 7837 (27) 10 808 (28) M1 80 (3) 282 (4) 907 (3) 1269 (3) Mx 1376 (55) 5095 (70) 20 141 (70) 26 612 (69) <0.001 Curative treatment No 1650 (66) 6532 (90) 25 343 (88) 33 525 (87) Yes 853 (34) 769 (10) 3542 (12) 5164 (13) <0.001 Specific death Alive 1060 (42) 3071 (42) 14 832 (51) 18 963 (49) UBC 533 (22) 1548 (21) 6284 (22) 8365 (22) OPC 536 (21) 1257 (17) 1919 (7) 3712 (10) Other cause 374 (15) 1425 (20) 5850 (20) 7649 (20) <0.001
cyclophosphamide and pelvic RT have been implicated as risk factors [10–12]. The situation is likely to be similar across countries where smoking is still a major risk factor for UBC and where guidelines for e.g. breast, gynaecological, prostate and colorectal cancers have implied adjuvant systemic treatments and/or RT to the pelvic region. As expected from that, a certain time at risk is needed to develop a second cancer, patients with OPC were older, and they also had a higher CCI because of older age and possibly previous sequelae from cancer treatment.
The different gender distribution between patients with synchronous and metachronous OPC and those with UBC only is explained for men by the common joint diagnoses of UBC and prostate cancer, with incident prostate cancer frequently detected during clinical examination and evaluation of the UBC diagnosis prior to RC or in the cystoprostatectomy specimen. Other studies have found similar, strong associations between UBC and prostate cancer
[13,14] and there may also be common biological pathways to the inception of these cancers [15,16]. In women, the increased risk for a metachronous cancer with a gynaecological cancer or with breast cancer plays a role. Previous treatments with cyclophosphamide for rheumatic diseases, breast cancer and other malignancies or RT for cervical or endometrial cancer have been implicated as risk factors for UBC [4,5,10,17–20]. In breast cancer, the wide indications for systemic adjuvant treatment also in early breast cancer with good prognosis give the opportunity for long induction times to have an effect after a previous, possibly carcinogenic exposure during a treatment episode. Previous cancer treatment may also limit the therapeutic arsenal for the UBC, e.g. by having reached maximum exposure to RT in the pelvic area.
The higher risk for patients with a clinically locally advanced UBC (clinical stage T2 and T3) to have a synchronous OPC might partly be explained by the use of more detailed staging Table 2 Probability in different strata of patient and tumour characteristics of receiving radical treatment with curative intent (RC/RT) for 5164 patients with UBC with synchronous or metachronous OPC, compared to patients with UBC only.
Variable,n (%) OPC+ UBC, n = 9804 (25%) UBC only, n = 28 885 (75%) Total, N = 38 689 Synchronous, n = 2503 (25%) Metachronous, n = 7301 (75%) Gender Male 802 (36) 462 (10) 2622 (12) 3886 (13) Female 51 (17) 307 (12) 920 (13) 1278 (13)
Age group, years
≤60 127 (49) 80 (16) 417 (9) 921 (16) 61–70 306 (43) 231 (15) 1247 (16) 1784 (18) 71–80 373 (35) 355 (13) 1302 (13) 2030 (15) >80 47 (10) 103 (4) 277 (4) 427 (5) Social status Unmarried 278 (32) 329 (11) 1383 (12) 1990 (13) Married 575 (35) 440 (10) 2159 (12) 3174 (14) Education Low 361 (31) 344 (10) 1538 (12) 2243 (13) Intermediate 331 (38) 270 (11) 1354 (13) 1955 (15) High 149 (37) 147 (12) 594 (12) 890 (14) Missing 12 (16) 8 (3) 56 (5) CCI 0 583 (46) 271 (13) 2663 (14) 3517 (16) 1 133 (42) 78 (11) 554 (10) 765 (12) 2 95 (17) 270 (11) 192 (9) 557 (11) ≥3 18 (9) 150 (7) 133 (7) 325 (7) Diagnosis period 1997–2001 126 (24) 149 (10) 864 (11) 1139 (12) 2002–2005 183 (36) 129 (9) 742 (12) 1054 (13) 2006–2010 280 (37) 223 (10) 1077 (13) 1580 (14) 2011–2014 264 (38) 268 (12) 859 (12) 1391 (14) cT-stage Tis, Ta, T1 169 (12) 132 (3) 560 (3) 861 (3) T2–4 676 (69) 628 (33) 2913 (42) 4217 (43) Tx 8 (12) 9 (5) 69 (10) 86 (9) cN-stage N0 529 (55) 440 (23) 2102 (26) 3071 (28) N+ 74 (57) 64 (28) 362 (36) 500 (37) Nx 250 (18) 265 (5) 1078 (5) 1593 (6) cM-stage M0 600 (57) 509 (26) 2458 (31) 3567 (33) M1 17 (21) 26 (9) 90 (10) 133 (10) Mx 236 (17) 234 (5) 994 (5) 1464 (6)
investigations such asfluorodeoxyglucose positron-emission tomography/CT to support clinical decision-making for patients with two malignancies; however, information about radiological investigations applied were not available in BladderBaSe. A concomitant diagnosis of an OPC related to simultaneous treatment of adjacent organs, such as prostate cancer in males treated with cystoprostatectomy [21] and
female genital cancer when hysterosalpingo-oophorectomy, as well as excision of the anterior vaginal wall as an integral part of RC in females, also contribute in patients with locally advanced UBC.
Our present investigation was partly driven by a concern that patients with metachronous or synchronous OPC would have been less actively treated and thus would have missed out on treatment opportunities. We noted a propensity to treat patients with metachronous T2–T4 or cN positive tumours less aggressively, but patients with earlier stages were treated very similarly in the three groups. Patients with a
synchronous OPC in the pelvic region were even more often offered treatment with curative intent than patients with UBC only, indicating that the patients’ UBC was actively treated despite two malignant diagnoses [21,22]. We do not hold data on the treatment of the OPC; case studies to review the quality of care for both tumours could provide information on important aspects of the management of these patients Despite the difference in treatment in the T2–T4 and cN strata, the multivariate models imply that stage by stage, the UBC-specific survival was similar between patients with synchronous OPC and those with UBC only. The survival analyses indicate that the policy to offer treatment with curative intent in a similar degree to patients with metachronous or synchronous OPC and to patients with UBC only was successful; the risk of dying from the UBC was similar in the three groups.
However, the OS was lower among those with synchronous OPC, mainly influenced by deaths from OPC with a bad prognosis, e.g. lung cancer. Thus, many patients with UBC and OPC with a known serious prognosis are very likely to experience recurrence from the OPC during follow-up of the UBC and will have a complicated disease trajectory. The high morbidity and resource-demanding management of the UBC together with management of recurrence of the OPC will require advanced multidisciplinary care. In this scenario, suboptimal treatment of the UBC is a disservice to patients. Table 3 Groups of UBC with OPC (synchronous/metachronous) in relation
to treatment modality. Total Treatment P Non-curative Curative Respiratory tract Synchronous 128 (24) 114 (24) 14 (24) Metachronous 415 (76) 370 (76) 45 (76) 1.000 Upper GI tract Synchronous 82 (32) 77 (33) 5 (19) Metachronous 177 (68) 155 (67) 22 (819 0.133 Lower GI tract Synchronous 198 (15) 156 (14) 42 (29) Metachronous 1087 (85) 984 (86) 103 (71) <0.001 Breast Synchronous 42 (6) 35 (6) 7 (7) Metachronous 631 (94) 542 (94) 89 (93) 0.646 Female genital Synchronous 42 (4) 30 (3) 12 (7) Metachronous 1164 (96) 1014 (97) 150 (93) 0.009 Male genital* Synchronous 1466 (40) 735 (28) 731 (74) Metachronous 2195 (60) 1935 (72) 260 (26) <0.001 Urinary tract Synchronous 332 (35) 293 (34) 39 (44) Metachronous 625 (65) 576 (66) 49 (56) 0.059 Skin/melanoma Synchronous 137 (9) 126 (9) 11 (7) Metachronous 1399 (91) 1259 (91) 140 (93) 0.548 Haematological Synchronous 68 (14) 58 (13) 10 (17) Metachronous 423 (86) 375 (87) 48 (83) 0.420 Endocrine/neuro Synchronous 15 (5) 13 (4) 2 (6) Metachronous 313 (95) 280 (96) 33 (94) 0.667 Other Synchronous 47 (26) 40 (24) 7 (26) Metachronous 149 (76) 129 (76) 20 (74) 0.810 UBC only 28 885 25 343 (88) 3542 (12) <0.001 Figures represent number of patients (% of the column).*Prostate cancer represents 97% of the patients.
Table 4 Relative hazards (RHs) for UBC-specific death for patients with synchronous or metachronous OPC as compared to patients with UBC only.
RH (95% CI) synchronous OPC RH (95% CI) synchronous OPC (excluding men with
synchronous prostate cancer)
RH (95% CI) metachronous OPC
All patients, UBC death 0.78 (0.71–0.87) NA 0.92 (0.85–0.99)
All patients, overall 1.01 (0.95–1.07) NA 1.01 (0.97–1.06)
Women, UBC death 0.89 (0.65–1.21) NA 0.89 (0.79–1.00)
Women, overall 1.27 (1.06–1.54) NA 1.01 (0.93–1.08)
Men, UBC death 0.78 (0.70–0.87) 1.07 (0.87–1.31) 0.95 (0.86–1.05)
Men, overall 0.99 (0.93–1.06) 1.46 (1.31–1.63) 1.01 (0.96–1.07)
Strengths And Limitations
The BladderBaSe has a high coverage, a complete follow-up through use of national registration numbers, and a detailed characterisation of patients due to extensive linkage [6]. The BladderBaSe is defined with the UBC as a starting point and currently there is no detailed information about stage of disease or treatment of the OPC. Thus, we could not study e.g. specifically the prognosis for patients where a previous cancer treatment may have induced the UBC, or the prognosis for patients with distant spread of the OPC at the time of UBC diagnosis. Likewise, we lacked information about smoking status, which might affect both UBC survival and risk of smoking-associated OPCs. There may be some misclassification for men with synchronous prostate cancer, where some who were initially reported as having prostate cancer may have had an extensive UBC and vice versa. However, our analyses without men with synchronous prostate cancer did not change the overall pattern.
Conclusion
An OPC is a common clinical problem in patients with UBC. Our present findings indicate that treatment for UBC after or in conjunction with an OPC carries just as high a probability of success as treatment in patients with UBC only. There are indications that treatment for UBC should be intensified in general, and the present study raises the hypothesis that treatment for patients with metachronous or synchronous OPC also should be intensified, and similar improvements in prognosis can result. Research into these patients’ needs and optimising their treatment considering their complicated disease trajectory is an important area of research in supportive care.
Acknowledgements
This work was supported by the Swedish Cancer Society (grant numbers CAN 2019/62 and CAN 2017/278). The
funding sources had no role in the study design, data analyses, interpretation or writing the manuscript.
Con
flicts Of Interest
None declared.
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Table 5 Vital status and causes of death in groups of OPC.
Living Death UBC Death OPC Death other causes All
Respiratory tract 149 (27) 111 (20) 175 (32) 108 (20) 543 (5.5) Upper GI 64 (25) 37 (14) 104 (40) 54 (21) 259 (2.6) Lower GI 507 (40) 259 (20) 245 (19) 274 (21) 1285 (13) Breast 296 (44) 168 (25) 95 (14) 114 (17) 673 (6.9) Female genital 544 (45) 304 (25) 147 (12) 211 (18) 1206 (12) Male genital* 1606 (48) 727 (20) 738 (20) 590 (16) 3661 (37) Urinary tract 459 (48) 117 (12) 231 (24) 150 (16) 957 (10) Skin/melanoma 619 (40) 389 (25) 173 (11) 355 (23) 1536 (16) Haematological 160 (33) 103 (21) 138 (28) 90 (18) 491 (5.0) Endocrine/neuro 169 (52) 65 (20) 36 (11) 58 (18) 328 (3.3) Other 63 (32) 48 (25) 49 (25) 36 (18) 196 (2.0) UBC only 14 832 (51) 6284 (22) 1919 (7) 5850 (20) 28 885 Median % 43 21 18 18
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Correspondence: Firas Aljabery, Department of Urology, Link€oping University, SE-581 58 Link€oping, Sweden. e-mail:firas.abdul-sattar.aljabery@regionostergotland.se Abbreviations: BladderBaSe, Bladder Cancer Data Base Sweden; CCI, Charlson Comorbidity Index; GI, gastro-intestinal; ICD, International Classification of Diseases; OPC, other primary cancers; OS, overall survival; RC, radical cystectomy; RT, radiotherapy; UBC, urinary bladder cancer.
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